As natural probes of living systems, viruses have provided some of the most fundamental insights into basic biological processes: DNA replication, transcription and translation, cell signaling pathways, oncogenes and tumor suppressors, and host immune defense. Their importance as agents of biowarfare and emerging infectious diseases, together with their potential for use as novel therapeutics in an age of molecular medicine, provided the impetus for the creation of the Center of Molecular and Tumor Virology (CMTV) at Louisiana State University Health Sciences Center-Shreveport in 2003. After four years of COBRE support we have laid the foundation for a world class virology center at an institution without a strong research tradition. The CMTV was built by aggressive faculty recruitment, diligent mentoring of young investigators, extensive partnering to create a sustainable research infrastructure, and melding COBRE goals with a newly formulated University strategic plan for long-range research development. With the CMTV now providing an element of strength that can be used to enhance the overall research mission campus-wide, we propose to broaden the impact of the requested COBRE support by 1) expansion of the CMTV beyond its original single departmental base to create synergistic scientific collaborations that are interdisciplinary, promote clinical applications of research findings, and involve three universities in North Louisiana and integrate COBRE and INBRE programs;2) mentored development of investigators previously funded by the COBRE, together with backing for five new Project Leaders whose multidisciplinary research is interconnected by a shared theme addressing the molecular basis for viral pathogenesis;3) enhancement of research infrastructure by the creation of COBRE Cores that fully integrate with and/or complement existing shared services. Together with the substantive University commitment to a revitalized mission that embraces biomedical research, this final phase of CMTV development will create a Center that is responsive to overall goals of the COBRE initiative and NIH Roadmap and is rooted in excellent basic science investigation with a translational emphasis that favors application of hypothesis-driven investigation from bench to bedside and back.